Phase I trial to study the effectiveness of bortezomib in treating patients who have recurrent glioma. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth

I. Determine the maximum tolerated dose of bortezomib with or without anticonvulsant drugs known to be metabolized by the P450 hepatic enzyme complex in patients with recurrent glioma.

II. Determine the biologic activity of this drug by measuring proteasome 20S activity in these patients.

III. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on biologic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent anticonvulsant drug use (phenytoin, carbamazepine, phenobarbital, primidone, or felbamate vs gabapentin, lamotrigine, valproic acid, or no anticonvulsant drugs).

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated with bortezomib at the MTD. Patients are followed every 2 months.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically confirmed progressive or recurrent malignant glioma

Anaplastic astrocytoma

Anaplastic oligodendroglioma

Glioblastoma multiforme

Prior low-grade gliomas that have progressed to high-grade after therapy allowed

Measurable disease by MRI or CT scan

Performance status - Karnofsky 60-100%

Absolute neutrophil count at least 1,500/mm^3

Platelet count at least 100,000/mm^3

Bilirubin no greater than 1.5 mg/dL

Transaminases no greater than 4 times upper limit of normal

Creatinine no greater than 1.7 mg/dL

Mini mental score at least 15

No concurrent serious infection or other medical illness that would preclude study participation

No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception during and for 3 months after study participation

At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

No more than 1 prior chemotherapy regimen

At least 3 months since prior radiotherapy and recovered

No other concurrent investigational agents

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006773